Phase 1/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK-1001 Administered Daily in Patients With Sickle Cell Disease

Phase 1

Completed

Brief Summary: The purpose of this study is to assess the safety and tolerability of HQK-1001 administered for a total of 12 weeks (with one dosing break) in subjects with sickle cell disease.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of SCD or sickle beta thalassemia (excluding Hemoglobin C)
Between 12 and 60 years of age, inclusive
At least one episode of a SCD-related crisis or complication (e.g., vaso-occlusive crisis, acute chest syndrome, priapism) per year for an average of 3 years or one episode of acute chest syndrome over the prior 5 years
Screening (untransfused) HbF level >/= 2% as analyzed by a central laboratory
If receiving hydroxyurea therapy, must be receiving a stable dose for at least 6 months
Able and willing to give informed consent
If female, must have a negative serum pregnancy test within 7 days of dosing
If female, must not be of childbearing potential defined as post-menopausal by at least 2 years or surgically sterile, or must agree to use a medically accepted form of contraception throughout the study
If the sexual partner of a male subject is a WCBP, she must agree to use a medically accepted form of birth control for themselves or their partner throughout the study
In the view of the Investigator, able to comply with necessary study procedures

Exclusion Criteria

Red blood cell (RBC) transfusion within 3 months prior to beginning study medication
Participation in a regular blood transfusion program
More than 4 hospitalizations for acute sickle cell-related events in the previous 12 months
An acute vaso-occlusive event within 3 weeks prior to receiving first dose of study medication
Pulmonary hypertension requiring oxygen
QTc > 450 msec on screening
Alanine transaminase (ALT) > 3X upper limit of normal (ULN)
Creatinine phosphokinase (CPK) > 20% above the ULN
Serum creatinine >1.2 mg/dL
An acute illness (e.g., febrile, gastrointestinal [GI], respiratory) within 72 hours prior to receiving first dose of study medication
History of syncope, clinically significant dysrhythmias or resuscitation from sudden death
Chronic opiate use which, in the view of the Investigator, could confound evaluation of an investigational drug
Current abuse of alcohol or drugs
Received another investigational agent within 4 weeks, or 5 half-lives, whichever is longer, prior to administration of study medication
Currently pregnant or breast feeding a child
Known infection with HIV-1
Infection with hepatitis B or hepatitis C such that patients are currently on therapy or will be placed on therapy during the trial

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Active	HQK-1001	-

Primary Outcome Measures

Name	Time	Method
Safety as assessed by (1) adverse events (2) laboratory values (3) vital signs, and (4) physical exam.	126 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics assessed by plasma drug concentration levels.	Days 0, 6, 69 and 97 post first dose
Pharmacodynamics assessed by red blood cell production and induction of fetal hemoglobin.	Every 2 weeks through Day 126 post first dose

Locations (9): Texas Children's Cancer Center and Hematology Service
🇺🇸
Houston, Texas, United States
Medical College of Georgia
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Augusta, Georgia, United States
Johns Hopkins School of Medicine
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Baltimore, Maryland, United States
Trialogic Research
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Madison, Alabama, United States
Children's Hospital and Research Center at Oakland
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Oakland, California, United States
UNC Comprehensive Sickle Cell Program
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Chapel Hill, North Carolina, United States
Century Clinical Research, Inc.
🇺🇸
Daytona Beach, Florida, United States
University of Illinois at Chicago
🇺🇸
Chicago, Illinois, United States
University of the West Indies, Mona
🇯🇲
Kingston, Mona, Jamaica